It is our theory that if we can better define the relative contributions of immune mechanisms in the inflammatory process in herpes simplex virus (HSV) stromal keratitis, then many unanswered questions concerning the pathogenesis of HSV ocular disease could be explained. Our overall objectives are to elucidate the immunoregulatory mechanisms in the pathogenesis of HSV disciform edema and deep stromal keratitis. Precise identification of the lymphocyte populations involved in tissue injury in HSV stromal keratitis may offer considerable knowledge on the basis for susceptibility to stromal disease as well as to the extent of intensity, duration and severity of disease. Our specific aims are to define the interrelationship between cell-mediated and humoral immune factors in the induction of the immunopathologic lesions of herpes HSV disciform and deep stromal keratitis in the rabbit cornea by delineating the role of separated and enriched subpopulations of T-cells, B-cells and macrophages in these conditions. The lymphocyte response findings will be compared with the clinical sequelae, corneal pathology, viral replication in the cornea, presence of HSV antigens in the corneal stroma and presence of immune complexes of viral antigen-antibody. The effects of immunosuppression on the course of HSV infection will be determined with respect to disciform edema and deep stromal keratitis. Clinical sequelae will be compared with cellular and humoral immune responses to HSV antigens, clearance of infectious HSV, presence of virus and viral antigens in the stroma, function of T-cell and B-cell responses to mitogens, and specific immune responses to thymus-dependent and thymus-independent antigens.